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1.
Lupus Sci Med ; 11(1)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589223

RESUMO

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.


Assuntos
Lúpus Eritematoso Sistêmico , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Lúpus Eritematoso Sistêmico/complicações , Estudos Prospectivos , Imunossupressores , Modelos Logísticos
2.
Semin Arthritis Rheum ; 65: 152378, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38310657

RESUMO

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.


Assuntos
Síndrome de Sjogren , Humanos , Resultado do Tratamento , Síndrome de Sjogren/terapia , Dor , Fadiga
3.
RMD Open ; 10(1)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38296310

RESUMO

OBJECTIVES: Real-world data regarding rheumatoid arthritis (RA) and its association with interstitial lung disease (ILD) is still scarce. This study aimed to estimate the prevalence of RA and ILD in patients with RA (RAILD) in Spain, and to compare clinical characteristics of patients with RA with and without ILD using natural language processing (NLP) on electronic health records (EHR). METHODS: Observational case-control, retrospective and multicentre study based on the secondary use of unstructured clinical data from patients with adult RA and RAILD from nine hospitals between 2014 and 2019. NLP was used to extract unstructured clinical information from EHR and standardise it into a SNOMED-CT terminology. Prevalence of RA and RAILD were calculated, and a descriptive analysis was performed. Characteristics between patients with RAILD and RA patients without ILD (RAnonILD) were compared. RESULTS: From a source population of 3 176 165 patients and 64 241 683 EHRs, 13 958 patients with RA were identified. Of those, 5.1% patients additionally had ILD (RAILD). The overall age-adjusted prevalence of RA and RAILD were 0.53% and 0.02%, respectively. The most common ILD subtype was usual interstitial pneumonia (29.3%). When comparing RAILD versus RAnonILD patients, RAILD patients were older and had more comorbidities, notably concerning infections (33.6% vs 16.5%, p<0.001), malignancies (15.9% vs 8.5%, p<0.001) and cardiovascular disease (25.8% vs 13.9%, p<0.001) than RAnonILD. RAILD patients also had higher inflammatory burden reflected in more pharmacological prescriptions and higher inflammatory parameters and presented a higher in-hospital mortality with a higher risk of death (HR 2.32; 95% CI 1.59 to 2.81, p<0.001). CONCLUSIONS: We found an estimated age-adjusted prevalence of RA and RAILD by analysing real-world data through NLP. RAILD patients were more vulnerable at the time of inclusion with higher comorbidity and inflammatory burden than RAnonILD, which correlated with higher mortality.


Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Adulto , Humanos , Estudos Retrospectivos , Prevalência , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Aprendizado de Máquina
4.
Molecules ; 28(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37959736

RESUMO

BACKGROUND: Lichens are complex symbiotic associations between a fungus and an alga or cyanobacterium. Due to their great adaptability to the environment, they have managed to colonize many terrestrial habitats, presenting a worldwide distribution from the poles to the tropical regions and from the plains to the highest mountains. In the flora of the Antarctic region, lichens stand out due to their variety and development and are a potential source of new bioactive compounds. METHODS: A phytochemical study of the Antarctic lichen Usnea aurantiaco-atra (Jacq) Bory was conducted with the intention of determining the most important metabolites. In addition, the cytotoxic and antioxidant activities of its extracts were determined. RESULTS: Cytotoxicity studies revealed that the hexane extract contains usnic acid as a majority metabolite, in addition to linoleic acid, ergosterols and terpenes, and demonstrates cytotoxic activity against an A375 melanoma cell line. On the other hand, the presence of total phenols in the extracts did not influence their antioxidant activity. CONCLUSIONS: U. aurantiaco-atra contains mainly usnic acid, although there are terpenes and ergosta compounds that could be responsible for its cytotoxic activity. The presence of phenols did not confer antioxidant properties.


Assuntos
Líquens , Usnea , Antioxidantes/química , Usnea/química , Líquens/química , Fenóis/química , Terpenos/metabolismo
5.
Semin Arthritis Rheum ; 61: 152232, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37348350

RESUMO

INTRODUCTION: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. OBJECTIVE: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. METHODS: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. RESULTS: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. CONCLUSIONS: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Nascimento Prematuro , Reumatologia , Gravidez , Humanos , Recém-Nascido , Feminino , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/epidemiologia , Síndrome Antifosfolipídica/complicações , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , beta 2-Glicoproteína I , Anticoagulantes , Imunoglobulina G , Imunoglobulina M
6.
Rheumatol Int ; 43(4): 735-741, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36436083

RESUMO

To verify, via a survey, the experience and needs of patients receiving methotrexate (MTX), their general management and the quality of the information provided by the rheumatologist. We conducted a 51-item online survey between May and July 2020 addressed to persons diagnosed with an immune-mediated disease and treated with MTX (regardless of the route of administration). Recruitment was done via Twitter. We obtained 294 responses, of which 283 were complete and could be analysed. Almost 82% of the respondents were women, 80% resided in Spain, 75% were between 31 and 60 years old, and 57% were active workers. Diseases included psoriasis (41%), lupus, Sjögren's or vasculitides (33%), and rheumatoid arthritis (16%), among others. Eighty per cent had read the leaflet inserted in the package, of whom 62% found it helpful. Only 15% of the respondents reported having been offered additional written material, which was considered barely functional (33 out of 100). Most patients (88%) responded that they had not received advice on any reliable sources to consult on the internet, and those who received it considered it unhelpful (24 out of 100). Patients receiving MTX due to an autoimmune disease demand more and better-quality written or web-based information than what is currently offered at their clinics.


Assuntos
Antirreumáticos , Artrite Reumatoide , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Metotrexato/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/diagnóstico , Inquéritos e Questionários , Reumatologistas , Resultado do Tratamento
7.
FEBS J ; 290(14): 3527-3532, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36349414

RESUMO

Self-assembling protein filaments are at the heart of cell function. Among them, tubulin-like proteins are essential for cell division, DNA segregation and cytoskeletal functions across the domains of life. FtsZ and tubulin share their core structures, a characteristic nucleotide-binding pocket and similar protofilament architecture. GTP hydrolysis between consecutive subunits drives their assembly dynamics. Two recent studies provide previously missing, filament atomic structures of bacterial FtsZ and a recently discovered archaeal tubulin in their nucleotide triphosphate-bound states. Both filament structures reveal strikingly conserved interfacial GTPase active sites, with Mg2+ and K+ /Na+ cations and an NxDxxD/E triad of catalytic residues, probably inherited from the common ancestor of FtsZs and tubulins. Moreover, both proteins exhibit nucleotide-regulated subunit association mediated by interfacial water bridges, as well as polymerization-induced structural changes, likely enabling related dynamic assembly mechanisms.


Assuntos
GTP Fosfo-Hidrolases , Tubulina (Proteína) , Tubulina (Proteína)/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Proteínas do Citoesqueleto/química , Archaea/genética , Archaea/metabolismo , Proteínas de Bactérias/metabolismo , Bactérias/metabolismo , Nucleotídeos , Guanosina Trifosfato/metabolismo
8.
Int J Mol Sci ; 23(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36232701

RESUMO

The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3'-5' exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR. We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan-Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy.


Assuntos
Fator de Ligação a CCAAT , Exorribonucleases , Neoplasias Hepáticas , Proteínas Mitocondriais , Polirribonucleotídeo Nucleotidiltransferase , Fator de Transcrição Sp1 , Sítios de Ligação , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/metabolismo , Exorribonucleases/genética , Exorribonucleases/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Luciferases/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Polirribonucleotídeo Nucleotidiltransferase/genética , Polirribonucleotídeo Nucleotidiltransferase/metabolismo , RNA Mensageiro/metabolismo , RNA Mitocondrial , RNA Interferente Pequeno , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
9.
Biomedicines ; 10(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36009372

RESUMO

The global spread of bacterial antimicrobial resistance is associated to millions of deaths from bacterial infections per year, many of which were previously treatable. This, combined with slow antibiotic deployment, has created an urgent need for developing new antibiotics. A still clinically unexploited mode of action consists in suppressing bacterial cell division. FtsZ, an assembling GTPase, is the key protein organizing division in most bacteria and an attractive target for antibiotic discovery. Nevertheless, developing effective antibacterial inhibitors targeting FtsZ has proven challenging. Here we review our decade-long multidisciplinary research on small molecule inhibitors of bacterial division, in the context of global efforts to discover FtsZ-targeting antibiotics. We focus on methods to characterize synthetic inhibitors that either replace bound GTP from the FtsZ nucleotide binding pocket conserved across diverse bacteria or selectively bind into the allosteric site at the interdomain cleft of FtsZ from Bacillus subtilis and the pathogen Staphylococcus aureus. These approaches include phenotype screening combined with fluorescence polarization screens for ligands binding into each site, followed by detailed cytological profiling, and biochemical and structural studies. The results are analyzed to design an optimized workflow to identify effective FtsZ inhibitors, and new approaches for the discovery of FtsZ-targeting antibiotics are discussed.

10.
Reumatol Clin (Engl Ed) ; 18(7): 393-398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35940672

RESUMO

INTRODUCTION: Nerve conduction studies (NCS) have been considered as the gold standard in carpal tunnel syndrome (CTS) diagnosis, despite correlation between clinical symptomatology and NCS severity has shown to be poor. In fact, clinical symptoms precede NCS changes in months or years. Few papers have been published about the clinical response to treatment of clinically typical CTS, but with normal NCS (NNCS). OBJECTIVE: To compare the clinical response to local corticosteroid injections (LCI) in clinically typical CTS, with NNCS and abnormal NCS (ANCS). METHOD: We included patients older than 18, with typical CTS symptoms (ongoing daily nocturnal pain/paresthesias in hand, at least during 3 months). Follow-up was done at 3, 6 and 12 months. Primary outcome was the visual analog scale for pain (p-VAS), comparing NNCS CTS wrists with ANCS CTS wrists. Statistic signification was established by the Student's t test, Mann-Whitney's "U", χ2 test and Yates' correction. RESULTS: We included 44 wrists in the NNCS group, and 83 in the ANCS group. There was no statistical significance between data in both groups, except in the 12-month follow-up, where the NNCS group achieved better results than the ANCS group in the 20% response (p=0.006). There was a trend toward a better 50% response in the 12-month follow-up. CONCLUSIONS: Our data suggest that LCI are similarly effective in both CTS with NNCS and ANCS. Nonetheless, there is a mild better effect in NNCS than in ANCS at 12-month follow-up.


Assuntos
Síndrome do Túnel Carpal , Corticosteroides/uso terapêutico , Síndrome do Túnel Carpal/tratamento farmacológico , Humanos , Injeções , Dor , Punho
11.
Reumatol Clin (Engl Ed) ; 18(4): 207-226, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443927

RESUMO

OBJECTIVE: To analyse the efficacy, adherence, patient satisfaction, safety, pharmacodynamics and cost-effectiveness of parenteral methotrexate (MTX) in patients with rheumatic diseases. METHODS: A systematic review of literature was carried out in Medline, Embase and Cochrane Central from the beginning until June 2019. Studies including adult patients with rheumatic diseases being treated with parenteral MTX were identified and data on efficacy, adherence, satisfaction, safety, pharmacokinetics, and cost-effectiveness analysed. As for the designs, systematic reviews, clinical trials, or observational studies were permitted, including cross-sectional and small-sample studies if they were pharmacokinetic studies. RESULTS: Out of 4160 identified articles, 80 articles were finally included. The efficacy profile of parenteral MTX seems useful in general and in those patients with insufficient response to oral MTX. The parenteral route does not seem to increase the rate or severity of adverse events due to the use of MTX. The use of parenteral MTX is an appropriate way to reduce costs in patients with inadequate response to oral MTX. Adherence and satisfaction are favoured by training programmes in the use of the parenteral route. The results in rheumatic diseases other than rheumatoid arthritis (RA) are very scarce and do not enable obtaining conclusive data. CONCLUSIONS: Parenteral MTX can be an alternative to the use of oral MTX, due to its profile of efficacy, safety, adherence and pharmacoeconomic results, especially in those patients with RA.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Reumáticas , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos Transversais , Humanos , Metotrexato/efeitos adversos , Doenças Reumáticas/tratamento farmacológico
12.
PLoS Biol ; 20(3): e3001497, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35312677

RESUMO

Treadmilling protein filaments perform essential cellular functions by growing from one end while shrinking from the other, driven by nucleotide hydrolysis. Bacterial cell division relies on the primitive tubulin homolog FtsZ, a target for antibiotic discovery that assembles into single treadmilling filaments that hydrolyse GTP at an active site formed upon subunit association. We determined high-resolution filament structures of FtsZ from the pathogen Staphylococcus aureus in complex with different nucleotide analogs and cations, including mimetics of the ground and transition states of catalysis. Together with mutational and biochemical analyses, our structures reveal interactions made by the GTP γ-phosphate and Mg2+ at the subunit interface, a K+ ion stabilizing loop T7 for co-catalysis, new roles of key residues at the active site and a nearby crosstalk area, and rearrangements of a dynamic water shell bridging adjacent subunits upon GTP hydrolysis. We propose a mechanistic model that integrates nucleotide hydrolysis signaling with assembly-associated conformational changes and filament treadmilling. Equivalent assembly mechanisms may apply to more complex tubulin and actin cytomotive filaments that share analogous features with FtsZ.


Assuntos
Proteínas do Citoesqueleto , Nucleotídeos , Proteínas de Bactérias/metabolismo , Proteínas do Citoesqueleto/metabolismo , Guanosina Trifosfato/metabolismo , Tubulina (Proteína)
13.
Rheumatology (Oxford) ; 61(11): 4427-4436, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-35166821

RESUMO

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.


Assuntos
Terapia Biológica , Imunossupressores , Humanos , Feminino , Adulto , Infliximab/uso terapêutico , Adalimumab/uso terapêutico , Etanercepte/uso terapêutico , Imunossupressores/uso terapêutico , Glucocorticoides , Resultado do Tratamento , Estudos Multicêntricos como Assunto
14.
Semin Arthritis Rheum ; 52: 151946, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35033377

RESUMO

BACKGROUND/OBJECTIVES: Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. METHODS: Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. RESULTS: The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00-13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84-7.25], p < 0.0002), valvulopathy (6.33 [3.41-11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16-1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07-16.86], p = 0.0015). Female sex (0.46 [0.25-0.88], p = 0.0147) and antimalarials (0.28 [0.17-0.45], p < 0.000) proved to be protective factors. CONCLUSIONS: Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.


Assuntos
Antimaláricos , COVID-19 , Insuficiência Cardíaca , Lúpus Eritematoso Sistêmico , Reumatologia , Antimaláricos/uso terapêutico , Estudos Transversais , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Sistema de Registros , SARS-CoV-2
15.
Hand (N Y) ; 17(4): 639-645, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-32757777

RESUMO

Background: In a previous paper, we have demonstrated that: (1) local injection of corticosteroids for carpal tunnel syndrome (CTS) is as effective as decompressive surgery, at 1-year follow-up; and (2) surgery has an additional benefit in the 2-year follow-up. In this study, we assess the long-term outcomes of both therapies in an observational extension of the patients originally enrolled in our randomized clinical trial. Methods: Patients were included in an open, randomized clinical trial, comparing injections versus surgery in CTS. After the end of the clinical trial, patients received the treatment prescribed by their general practitioner or specialist. Therapeutic failure was defined as the need of any new therapeutic intervention on the involved wrist. Comparison between groups was made using Cox multiple regression analysis. Estimation of the accumulated incidence of new therapeutic failure was made considering the withdrawal as a competitive risk (Gooley's test). Results: Of 163 randomized wrists at the beginning of the study, only 148 were available at the final follow-up. The mean follow-up was 6.3 and the median was 5.9 years. In the long-term follow-up, the accumulated incidence of therapeutic failure in the surgery group was 11.6% versus 41.8% in the injection group. The Cox multiple regression analysis showed a risk of failure associated with injection group of 4.5 (95% confidence interval [CI], 2.1-9.8; P < .0001). Conclusions: In long-term follow-up, surgery seems more effective than local corticosteroid injections in primary CTS. Nonetheless, about 58% of the patients in the injection group will not need further therapeutic interventions during the follow-up.


Assuntos
Síndrome do Túnel Carpal , Corticosteroides/uso terapêutico , Síndrome do Túnel Carpal/tratamento farmacológico , Síndrome do Túnel Carpal/cirurgia , Humanos , Injeções , Esteroides
16.
Musculoskeletal Care ; 20(1): 158-166, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34236743

RESUMO

OBJECTIVE: To investigate the barriers and facilitators of adherence to methotrexate (MTX) in people with rheumatic diseases and to explore the experience of shared decision-making. METHODS: A qualitative study was carried out. People diagnosed with inflammatory arthritides or systemic autoimmune diseases and who were treated with MTX were invited to participate in focus groups. The discourse was coded and synthesised with a content analysis approach. RESULTS: The groups included 12 representative patients (rheumatoid arthritis, spondylarthritis, and systemic lupus erythematosus, taking either oral or subcutaneous MTX). Four main themes were identified: (1) drug-related aspects (package insert, adverse events, administration, and difficulties with treatment); (2) patient-physician relationship; (3) social environment (lack of visibility of rheumatic diseases and the support of patient associations); and (4) medication and medical care practicalities (information, reliable sources, and expanding knowledge in other health areas). CONCLUSIONS: Aspects identified might help improve adherence, including quality information, especially on adverse events, the role of the setting, and shared decision-making.


Assuntos
Antirreumáticos , Artrite Reumatoide , Doenças Reumáticas , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Grupos Focais , Humanos , Metotrexato/uso terapêutico , Pesquisa Qualitativa , Doenças Reumáticas/tratamento farmacológico
17.
Artigo em Inglês | MEDLINE | ID: mdl-34501890

RESUMO

HIV/AIDS stigma is a global issue and a serious problem in African countries. Although prevalence remains high in this region, no detailed study has yet been carried out to determine and characterize this problem in Burundi. Using a qualitative analysis based on an extensive series of 114 interviews, we describe the main characteristics of HIV stigma in the country. The results of our study indicate that the problem of HIV/AIDS stigma is widespread in Burundian society, as all participants in the research reported having experienced some kind of HIV stigma. The seven dimensions of stigma identified in people living with HIV/AIDS (PLWHA) in Burundi are physical violence, verbal violence, marginalization, discrimination, self-stigma, fear and insecurity, and healthcare provider stigma. These dimensions of stigma can be experienced through different manifestations, which have been characterized in this study, revealing that the problem of stigma in PLWHA is still an important issue in Burundi.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Síndrome da Imunodeficiência Adquirida/epidemiologia , Burundi/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Pesquisa Qualitativa , Estigma Social
18.
Biophys Rev ; 13(4): 459-484, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34471434

RESUMO

Dr. Serge N. Timasheff, our mentor and friend, passed away in 2019. This article is a collection of tributes from his postdoctoral fellows, friends, and daughter, who all have been associated with or influenced by him or his research. Dr. Timasheff is a pioneer of research on thermodynamic linkage between ligand interaction and macromolecular reaction. We all learned a great deal from Dr. Timasheff, not only about science but also about life.

19.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34147354

RESUMO

INTRODUCTION: Nerve conduction studies (NCS) have been considered as the gold standard in carpal tunnel syndrome (CTS) diagnosis, despite correlation between clinical symptomatology and NCS severity has shown to be poor. In fact, clinical symptoms precede NCS changes in months or years. Few papers have been published about the clinical response to treatment of clinically typical CTS, but with normal NCS (NNCS). OBJECTIVE: To compare the clinical response to local corticosteroid injections (LCI) in clinically typical CTS, with NNCS and abnormal NCS (ANCS). METHOD: We included patients older than 18, with typical CTS symptoms (ongoing daily nocturnal pain/paresthesias in hand, at least during 3 months). Follow-up was done at 3, 6 and 12 months. Primary outcome was the visual analog scale for pain (p-VAS), comparing NNCS CTS wrists with ANCS CTS wrists. Statistic signification was established by the Student's t test, Mann-Whitney's "U", χ2 test and Yates' correction. RESULTS: We included 44 wrists in the NNCS group, and 83 in the ANCS group. There was no statistical significance between data in both groups, except in the 12-month follow-up, where the NNCS group achieved better results than the ANCS group in the 20% response (p=0.006). There was a trend toward a better 50% response in the 12-month follow-up. CONCLUSIONS: Our data suggest that LCI are similarly effective in both CTS with NNCS and ANCS. Nonetheless, there is a mild better effect in NNCS than in ANCS at 12-month follow-up.

20.
Rev. colomb. reumatol ; 28(2): 152-155, abr.-jun. 2021. graf
Artigo em Espanhol | LILACS | ID: biblio-1357262

RESUMO

RESUMEN Los nódulos reumatoides benignos son nódulos subcutáneos, idénticos en su morfología e histología a los que ocurren en el transcurso de la artritis reumatoide (AR), que aparecen en personas sin síntomas de artritis y con factor reumatoide (FR) negativo. Se presenta el caso de un varón de 46 arios de raza caucasiana que consultó por tumoración en la pierna derecha. Destacaba negatividad de factor reumatoide, anticuerpos anti péptido citrulinado, anticuerpos antinucleares y anticuerpos anticitoplasma de neutrófilo, así como normalidad de los reactantes de fase aguda. Una ecografía musculoesquelética mostró una tumoración sólida de 3,5 x 1,5 cm, de márgenes bien definidos, en músculo sóleo, con una estructura heterogénea hipoecoica con vascularización intra y perilesional. La resonancia magnética evidenció una tumoración de carácter fibroso sin datos sugestivos de agresividad. Una biopsia guiada por ecografía mostró histología característica de nódulo reumatoide. Se discuten la clínica, el diagnóstico, el diagnóstico diferencial y el tratamiento de los nódulos reumatoides benignos.


ABSTRACT Benign rheumatoid nodules are subcutaneous nodules, identical in morphology and histo logy to those that occur in the course of rheumatoid arthritis. They appear in people without symptoms of arthritis and with negative rheumatoid factor. The case is presented of a 46-year-old Caucasian man who consulted for a tumour inthe right leg. He was negative for rheumatoid factor, anti-citrullinated protein antibodies, antinuclear antibodies, and antineutrophil cytoplasmic antibodies, as well as for acute phase reactants. A musculoskeletal ultrasound showed a solid tumour of 3.5 × 1.5 cm with well-defined margins in the soleus muscle, and with a heterogeneous hypoechoic structure with intra- and peri-lesional vascularisation. The magnetic resonance imaging showed a fibrous tumour with no signs suggestive of aggressive growth. An ultrasound-guided biopsy sho wed the characteristic histology of the rheumatoid nodule. The clinical picture, diagnosis, differential diagnosis, and treatment of benign rheumatoid nodules are discussed.


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Artrite Reumatoide , Nódulo Reumatoide , Doenças Musculoesqueléticas
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